Methods and systems for treating restenosis sites using electroporation
A system is provided for reducing restenosis. A catheter apparatus is provided with at least first and second mono-polar electrodes positioned at an inflatable balloon. The balloon is sized to be positioned and expanded at a restenosis site. A voltage pulse generator is coupled to the first and second mono-polar electrodes. The voltage pulse generator is configured to apply an electric field, in a controlled manner, to the restenosis site in an amount sufficient to produce electroporation of the restenosis site, and below an amount that causes thermal damage to the restenosis site.
1 . A system for reducing restenosis, comprising:
a catheter apparatus including at least first and second mono-polar electrodes positioned at an inflatable balloon, the balloon being sized to be positioned and expanded at a restenosis site;
a voltage pulse generator coupled to the first and second mono-polar electrodes and configured to apply an electric field in a controlled manner to the restenosis site in an amount sufficient to produce electroporation of the restenosis site and below an amount that causes thermal damage to the restenosis site.
2 . The system of claim 1 , further comprising:
a monitoring electrode configured to measure a test voltage delivered to cells in the restenosis site.
3 . The system of claim 1 , wherein the test voltage is insufficient to create irreversible electroporation.
4 . The system of claim 1 , wherein the first and second mono-polar electrodes are band electrodes that extend at least partially circumferentially around the balloon.
5 . The system of claim 4 , wherein sufficient band electrodes are provided to create electroporation along a length of the restenonsis site.
6 . The system of claim 1 , wherein the electroporation is performed in a controlled manner with real time monitoring.
7 . The system of claim 1 , wherein the electroporation is performed in a controlled manner to provide for controlled pore formation in cell membranes.
8 . The system of claim 1 , wherein the electroporation is performed in a controlled manner to create a tissue effect of cells at the restenosis site while preserving surrounding tissue.
9 . The system of claim 1 , wherein the electroporation is performed in a controlled manner with monitoring of electrical impedance;
10 . The system of claim 1 , further comprising:
detecting an onset of electroporation of cells at the restenosis tissue site.
11 . The system of claim 1 , wherein the electroporation is performed in a controlled manner with controlled intensity and duration of voltage.
12 . The system of claim 1 , wherein the electroporation is performed in a controlled manner with real time control.
13 . The system of claim 1 , wherein the electroporation is performed in a manner to for modification and control of mass transfer across cell membranes.
14 . The system of claim 1 , wherein the electroporation is performed in a controlled manner with a proper selection of voltage magnitude.
15 . The system of claim 1 , wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.
16 . The system of claim 1 , wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 5 microseconds to about 62 seconds.
17 . The system of claim 1 , wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 90 to 110 microseconds.
18 . The system of claim 1 , wherein the voltage pulse generator is configured to provide that each pulse is applied for about 100 microseconds.
19 . The system of claim 17 , wherein the voltage pulse generator is configured to apply from about 1 to 15 pulses.
20 . The system of claim 17 , wherein the voltage pulse generator is configured to apply about eight pulses of about 100 microseconds each in duration.
21 . The system of claim 1 , wherein the voltage pulse generator is configured to provide for pulse application to produce a voltage gradient at the restenosis tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.
22 . The system of claim 1 , wherein a temperature of the restenosis tissue site is monitored and the pulses are adjusted to maintain a temperature of 100 degrees C. or less at the restenosis tissue site.
23 . The system of claim 1 , wherein a temperature of the restenosis tissue site is monitored and the pulses are adjusted to maintain a temperature of 75 degrees C. or less at the restenosis tissue site.
24 . The system of claim 1 , wherein a temperature of the restenosis tissue site is monitored and the pulses are adjusted to maintain a temperature of 60 degrees C. or less at the restenosis tissue site.
25 . The system of claim 22 , wherein the temperature is maintained at 50 degrees C. or less.
26 . The system of claim 1 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 100 degrees C. or less.
27 . The system of claim 1 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 75 degrees C. or less.
28 . The system of claim 1 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 60 degrees C. or less.
29 . The system of claim 1 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 50 degrees C. or less.
30 . The system of claim 1 , wherein the first electrode is placed at about 5 mm to 10 cm from the second electrode.
31 . The system of claim 1 , wherein the first and second mono-polar electrodes are circular in shape.
32 . The system of claim 1 , wherein the voltage pulse generator is configured to provide for pulse application of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the restenosis tissue site.
33 . The system of claim 1 , wherein a ratio of electric current through cells at the restenosis tissue site to voltage across the cells is detected and a magnitude of applied voltage to the restenosis tissue site is adjusted in accordance with changes in the ratio of current to voltage.
34 . A system for reducing restenosis, comprising:
a catheter apparatus including a bi-polar electrode positioned at a inflatable balloon, the balloon being sized to be positioned and expanded at a restenosis site;
a voltage pulse generator coupled to the bi-polar electrode and configured to apply an electric field in a controlled manner to the restenosis site in an amount sufficient to produce electroporation of the restenosis site and below an amount that causes thermal damage to the restenosis site.
35 . The system of claim 34 , further comprising:
a monitoring electrode configured to measure a test voltage delivered to cells in the restenosis site.
36 . The system of claim 34 , wherein the test voltage is insufficient to create irreversible electroporation.
37 . The system of claim 34 , wherein the bipolar electrode is a band electrode that extend at least partially circumferentially around the balloon.
38 . The system of claim 4 , wherein sufficient band electrodes are provided to create electroporation along a length of the restenonsis site.
39 . The system of claim 34 , further comprising:
a second bi-polar electrode.
40 . The system of claim 39 , wherein the bi-polar electrodes are band electrodes that extend at least partially circumferentially around the balloon.
41 . The system of claim 34 , wherein the electroporation is performed in a controlled manner with real time monitoring.
42 . The system of claim 34 , wherein the electroporation is performed in a controlled manner to provide for controlled pore formation in cell membranes.
43 . The system of claim 34 , wherein the electroporation is performed in a controlled manner to create a tissue effect of cells at the restenosis site while preserving surrounding tissue.
44 . The system of claim 34 , wherein the electroporation is performed in a controlled manner with monitoring of electrical impedance;
45 . The system of claim 34 , further comprising:
detecting an onset of electroporation of cells at the restenosis site.
46 . The system of claim 34 , wherein the electroporation is performed in a controlled manner with controlled intensity and duration of voltage.
47 . The system of claim 34 , wherein the electroporation is performed in a controlled manner with real time control.
48 . The system of claim 34 , wherein the electroporation is performed in a manner to for modification and control of mass transfer across cell membranes.
49 . The system of claim 34 , wherein the electroporation is performed in a controlled manner with a proper selection of voltage magnitude.
50 . The system of claim 34 , wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.
51 . The system of claim 34 , wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 5 microseconds to about 62 seconds.
52 . The system of claim 34 , wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 90 to 110 microseconds.
53 . The system of claim 34 , wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 100 microseconds.
54 . The system of claim 52 , wherein the voltage pulse generator is configured to apply from about 1 to 15 pulses.
55 . The system of claim 52 , wherein the voltage pulse generator is configured to apply about eight pulses of about 100 microseconds each in duration.
56 . The system of claim 34 , wherein the voltage pulse generator is configured to provide for pulse application to produce a voltage gradient at the restenosis tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.
57 . The system of claim 34 , wherein a temperature of the restenosis tissue site is monitored and the pulses are adjusted to maintain a temperature of 100 degrees C. or less at the restenosis tissue site.
58 . The system of claim 34 , wherein a temperature of the restenosis tissue site is monitored and the pulses are adjusted to maintain a temperature of 75 degrees C. or less at the restenosis tissue site.
59 . The system of claim 34 , wherein a temperature of the restenosis tissue site is monitored and the pulses are adjusted to maintain a temperature of 60 degrees C. or less at the restenosis tissue site.
60 . The system of claim 57 , wherein the temperature is maintained at 50 degrees C. or less.
61 . The system of claim 34 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 100 degrees C. or less.
62 . The system of claim 34 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 75 degrees C. or less.
63 . The system of claim 34 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 60 degrees C. or less.
64 . The system of claim 34 , wherein a current-to-voltage ratio is adjusted based on temperature to maintain the restenosis tissue site temperature at 50 degrees C. or less.
65 . The system of claim 34 , wherein the voltage pulse generator is configured to provide for pulse application of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the restenosis tissue site.
66 . The system of claim 34 , wherein a ratio of electric current through cells at the restenosis tissue site to voltage across the cells is detected and a magnitude of applied voltage to the restenosis tissue site is adjusted in accordance with changes in the ratio of current to voltage.
67 . A method for reducing restenosis, comprising:
introducing a balloon with first and second mono-polar electrodes through vasculature to a restenosis site;
positioning the balloon and the first and second mono-polar electrodes at or near the restenosis site;
applying an electric field in a controlled manner to the restenosis site in an amount sufficient to produce electroporation of the restenosis site and below an amount that causes thermal damage to the restenosis site.
68 . The method of claim 67 , further comprising:
using a monitoring electrode to measure a test voltage delivered to cells in the restenosis site.
69 . The method of claim 66 , wherein the test voltage is insufficient to create irreversible electroporation.
70 . The method of claim 67 , wherein the first and second mono-polar electrodes are band electrodes at least partially circumferentially positioned around the balloon.
71 . The method of claim 70 , wherein sufficient band electrodes are provided to create electroporation along a length of the restenonsis site.
72 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner with real time monitoring.
73 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner to provide for controlled pore formation in cell membranes.
74 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner to create a tissue effect of cells at the restenosis site while preserving surrounding tissue.
75 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner with monitoring of electrical impedance;
76 . The method of claim 67 , further comprising:
detecting an onset of electroporation of cells at the restenosis site.
77 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner with controlled intensity and duration of voltage.
78 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner with real time control.
79 . The method of claim 67 , further comprising:
performing the electroporation in a manner for modification and control of mass transfer across cell membranes.
80 . The method of claim 67 , further comprising:
performing the electroporation in a controlled manner with a proper selection of voltage magnitude.
81 . The method of claim 67 , wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.
82 . The method of claim 67 , wherein the duration of each pulse is about 5 microseconds to about 62 seconds.
83 . The method of claim 67 , wherein the duration of each pulse is about 90 to 110 microseconds.
84 . The method of claim 67 , wherein the duration of each pulse is about 100 microseconds.
85 . The method of claim 83 , wherein about 1 to 15 pulses are applied.
86 . The method of claim 83 , wherein about eight pulses of about 100 microseconds each in duration are applied.
87 . The method of claim 67 , wherein pulses are applied to produce a voltage gradient at the restenosis tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.
88 . The method of claim 67 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 100 degrees C. or less at the restenosis tissue site.
89 . The method of claim 67 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 75 degrees C. or less at the restenosis tissue site.
90 . The method of claim 67 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 60 degrees C. or less at the restenosis tissue site.
91 . The method of claim 67 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 50 degrees C. or less at the restenosis tissue site.
92 . The method of claim 67 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 100 degrees C. or less.
93 . The method of claim 67 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 75 degrees C. or less.
94 . The method of claim 67 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 60 degrees C. or less.
95 . The method of claim 67 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 50 degrees C. or less.
96 . The method of claim 67 , wherein the pulses applied are of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the restenosis tissue site.
97 . The method of claim 67 , wherein a ratio of electric current through cells at the restenosis tissue site to voltage across the cells is detected and a magnitude of applied voltage to the restenosis tissue site is adjusted in accordance with changes in the ratio of current to voltage.
98 . A method for reducing restenosis, comprising:
introducing a balloon with a bi-polar electrode through vasculature to a restenosis site;
positioning the balloon and the bi-polar electrode at or near the restenosis site;
applying an electric field in a controlled manner to the restenosis site in an amount sufficient to produce electroporation of the restenosis site and below an amount that causes thermal damage to the restenosis site.
99 . The method of claim 98 , further comprising:
using a monitoring electrode to measure a test voltage delivered to cells in the restenosis site.
100 . The method of claim 99 , wherein the test voltage is insufficient to create irreversible electroporation.
101 . The method of claim 101 , wherein the bi-polar electrode is a band electrode at least partially circumferentially positioned around the balloon.
102 . The method of claim 98 , wherein sufficient band electrodes are provided to create electroporation along a length of the restenonsis site.
103 . The method of claim 98 , further comprising:
a second bi-polar electrode.
104 . The method of claim 103 , wherein the bi-polar electrodes are band electrodes at least partially circumferentially positioned around the balloon.
105 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner with real time monitoring.
106 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner to provide for controlled pore formation in cell membranes.
107 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner to create a tissue effect of cells at the restenosis site while preserving surrounding tissue.
108 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner with monitoring of electrical impedance;
109 . The method of claim 98 , further comprising:
detecting an onset of electroporation of cells at the restenosis site.
110 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner with controlled intensity and duration of voltage.
111 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner with real time control.
112 . The method of claim 98 , further comprising:
performing the electroporation in a manner for modification and control of mass transfer across cell membranes.
113 . The method of claim 98 , further comprising:
performing the electroporation in a controlled manner with a proper selection of voltage magnitude.
114 . The method of claim 98 , wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.
115 . The method of claim 98 , wherein the duration of each pulse is about 5 microseconds to about 62 seconds.
116 . The method of claim 98 , wherein the duration of each pulse is about 90 to 110 microseconds.
117 . The method of claim 98 , wherein the duration of each pulse is about 100 microseconds.
118 . The method of claim 116 , wherein about 1 to 15 pulses are applied.
119 . The method of claim 116 , wherein about eight pulses of about 100 microseconds each in duration are applied.
120 . The method of claim 98 , wherein pulses are applied to produce a voltage gradient at the restenosis tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.
121 . The method of claim 98 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 100 degrees C. or less at the restenosis tissue site.
122 . The method of claim 98 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 75 degrees C. or less at the restenosis tissue site.
123 . The method of claim 98 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 60 degrees C. or less at the restenosis tissue site.
124 . The method of claim 98 , further comprising:
monitoring a temperature of the restenosis tissue site; and
adjusting the pulses to maintain a temperature of 50 degrees C. or less at the restenosis tissue site.
125 . The method of claim 98 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 100 degrees C. or less.
126 . The method of claim 98 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 75 degrees C. or less.
127 . The method of claim 98 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 60 degrees C. or less.
128 . The method of claim 98 , further comprising:
adjusting a current-to-voltage ratio based on temperature to maintain the restenosis tissue site temperature at 50 degrees C. or less.
129 . The method of claim 98 , wherein the pulses applied are of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the restenosis tissue site.
130 . The method of claim 98 , wherein a ratio of electric current through cells at the restenosis tissue site to voltage across the cells is detected and a magnitude of applied voltage to the restenosis tissue site is adjusted in accordance with changes in the ratio of current to voltage.